PWWP2B

Chr 10

PWWP domain containing 2B

Also known as: PWWP2, bA432J24.1, pp8607

NCBI Gene: 170394 ENSG00000171813 UniProt: Q6NUJ5 OMIM: 621586

PWWP2B encodes a chromatin-binding protein that acts as an adapter between nucleosome components and chromatin-modifying complexes, regulating histone acetylation levels at actively transcribed genes by forming NuRD subcomplexes and recruiting HDACs to gene promoters. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables NuRD complex binding activity. Predicted to be involved in chromatin remodeling; positive regulation of transcription elongation by RNA polymerase II; and regulation of cold-induced thermogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.841

Z-score 2.28

OE 0.00 (0.00–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.42Z-score

OE missense 0.81 (0.74–0.88)

338 obs / 419.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.49)

0≤0.351.4

Missense OE?0.81 (0.74–0.88)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 0 / 6.0Missense obs/exp: 338 / 419.6Syn Z: -1.92

Background carrier burden — how many people carry a rare variant somewhere in PWWP2B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

909 rare PASS variants

Rare truncating (LoF)

1 in 2,600

94 rare PASS variants

Rare synonymous (reference)

1 in 41

490 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PWWP2B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 54	1 in 2,300
South Asian	~43k	1 in 43	1 in 2,000
Remaining (unassigned)	~30k	1 in 38	1 in 3,000
European (Finnish)	~27k	1 in 94	1 in 2,700
Admixed American	~22k	1 in 52	1 in 820
African / African American	~21k	1 in 47	1 in 1,100
East Asian	~20k	1 in 58	≈ 1 in 5,900
Ashkenazi Jewish	~13k	1 in 120	≈ 1 in 5,700
Middle Eastern	~2,884	1 in 60	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 1 of 2 (exon 1 below).? see exons ↓